The Orofacial Pain Research

Chronic musculoskeletal pains are among the commonest reasons for longtime disability and thus are associated with high costs for the society.

Malin Ernberg’s group gathered in front of a poster at the International Association for the Study of Pain Congress in Boston 2018.
The research group of Malin Ernberg. Photo: N/A

In the orofacial area temporomandibular disorders (TMD) are the most frequent chronic pain conditions. TMD is a collective term embracing chronic conditions affecting the temporomandibular joint (TMJ) or the masticatory muscles (myalgia). It affects about 5%–10% of the population and is more prevalent in women than men. In children prevalence as high as 20% has been reported. Symptoms include pain especially on function, tenderness, restricted jaw opening, joint sounds and locking as well as headache and, thus, reduces patients’ quality of life.

The main focus of the research is on orofacial pain of muscular origin, from causes to treatment in both children and adults, and its sex differences. Another area is orofacial pain in children with juvenile Idiopathic arthritis. The group also conduct pedagogic research.

The research is translational, spanning from basic research conducted in patients and matched pain-free controls via human experimental studies where pain is induced experimentally, to clinical intervention studies. The research methods include e.g. intramuscular microbiopsy, microdialysis, blood and saliva sampling for immunohistochemistry, biochemical, genomic and proteomic analyses (in collaboration with other researchers), conditioned pain modulation, exercise-induced analgesia, quantitative sensory testing (sensory and pain thresholds for warmth, cold and mechanical stimuli), transcranial magnetic stimulation (TMS), electromyography (EMG) and jaw tracking.

The Orofacial Pain Research Group is part of the larger Orofacial Neuroscience Group at the Department of Dental Medicine, which in turn collaborates with other leading research groups in Malmö and Aarhus, via the Scandinavian Center for Orofacial Neuroscience (SCON). The group also has a close collaboration with the Specialist Clinic for Orofacial Pain at the Eastman Institute in Stockholm. Group members and projects follow below.

Group members

  • Malin Ernberg, DDS, PhD, professor
  • Nikolaos Christidis, DDS, PhD, associate professor
  • Britt Hedenberg-Magnusson, DDS, PhD, associate professor
  • Sofia Louca Jounger, DDS, PhD
  • Hajer Jasim, DDS, PhD
  • Samaa Al Sayegh, DDS, PhD Student
  • Abdelrahman Alhilou, DDS, MSci, PhD Student
  • Malin Collin, DDS, PhD Student
  • Golnaz Barjandi, DDS, PhD student
  • Maria Erkapers, DDS, PhD student
  • Ioanna Vasilatou, DDS, MSci student
  • Raghdah Abduljabbar, DDS, MSci student

Pain genes and muscle biomarkers in TMD myalgia

Close-up of patient with a thin catheter that goes into his cheek and another one that goes out of the cheek.
Intramuscular microdialysis of the masseter. This is a method developed by us that allows the collection of different substances from the extracellular environment in-vivo. A hollow catheter is inserted into the masseter muscle and slowly perfused with a buffered saline solution via a transparent tubing. Through a permeable membrane at the end of the catheter, molecules in the muscle tissue diffuse inti the perfusion fluid and are collected via a red tubing into small vials for later analysis. Photo: Malin Ernberg

PI: Malin Ernberg

In this clinical/experimental study we investigate the role of algogenic inflammatory markers and their genes in the pathophysiology underlying TMD myalgia in clinical and experimental studies using e.g. intramuscular microdialysis, blood and saliva samples. The project started 2010 and has so far resulted in a PhD thesis with several publications.

Group members: Sofia Louca Jounger, Nikolaos Christidis

Collaborations: Professor Martin Schalling, KI; Professor Peter Svensson, Aarhus University.

Molecular biomarkers in saliva in health and pain states

Photo of gel showing protein expression in saliva of a patients with TMD myalgia and an age and sex-matched healthy contro
Gel showing protein expression in saliva of a patients with TMD myalgia and an age and sex-matched healthy control. The proteins are expressed as dark bands; the darker the band is the higher is the expression. At a group level, several proteins involved in stress-, immune- and defense responses, as well as metabolic processes differ compared to the control, being either up- or down-regulated. Photo: Hajer Jasim

PI: Malin Ernberg

The overall aim is to investigate saliva levels of algesic and inflammatory markers in TMD pain. Saliva levels of 5-HT, glutamate, nerve growth factor (NGF), substance P (SP), calcitonin gene-related peptide (CGRP), and brain derived neurotrophic factor (BDNF) as well as the whole proteome is compared between patients with TMD myalgia and healthy controls. The project started 2012 and has so far resulted in a PhD thesis with several methodological and clinical publications.

Group members: Hajer Jasim, Britt Hedenberg-Magnusson

Collaboration: Associate Professor Bijar Ghafouri and Professor Björn Gerdle, Linköping University, Sweden; Professor Jochen Schwenk and PhD Claudia Fredolini, Royal Institute of Technology, Stockholm, Sweden.

    The role of the kynurenine pathway and oral microbiota in chronic muscle pain

    PI: Malin Ernberg

    The aim of this project is to explore if a shift in the tryptophan metabolism and salivary microbiome participates in the pathogenesis of chronic musculoskeletal pain and includes patients with TMD myalgia and myofascial pain as well as fibromyalgia. Methods involve intramuscular microdialysis and blood samples that are analyzed with novel techniques. The project started 2018.

    Group members: Golnaz Barjandi, Britt Hedenberg-Magnusson

    Collaboration: Professor Eva Kosek, Professor Sophie Erhardt and Professor Georgios Belibasakis, KI.

    Jaw motor control in patients with severe tooth wear

    PI: Malin Ernberg

    The project aims to investigate different aspects of jaw motor control, jaw function and oral health impact on quality of life in patients with severe tooth wear before and after comprehensive oral rehabilitation. In this project, novel technologies are used influences from a prosthetic intervention concerning parafunction, temporomandibular symptoms, and oral health impact on quality of life is unclear and is desirable to clarify. The project started 2019.

    Group members: Maria Erkapers

    Collaborations: Professor Peter Svensson, Aarhus University; PhD Susanna Segerström, Uppsala University.  

    Expression of pain receptors and proteomics in healthy and painful human muscle tissue

      The researcher Nikolaos Christidis himself with a needle in his cheek.
      The microbiopsies are obtained through the skin-surface overlaying the superficial masseter muscle. 30 min before this procedure topical anesthesia (EMLA®, 25mg lidocaine and 25 mg prilocaine, AstraZeneca, Södertälje, Sweden) will be placed over the skin at the area to be penetrated. A Bard®TruGuide™ coaxial needle (BARD Norden, Helsingborg, Sweden) will be inserted to a depth of 10 mm and used to guide the biopsy instrument (Bard® Monopty® disposable core biopsy instrument with a penetration depth of 11 mm and a diameter of 18G). Photo: Per Alstergren

      PI: Nikolaos Christidis

      The aim of the project is to investigate if muscle pain is associated with changes in expression of peripheral pain receptors and the muscle proteome. The project includes clinical and human experimental studies in which muscle microbiopsies are taken and analyzed with immunohistochemistry, in-situ hybridization and proteomics. The project started 2015.

      Group members: Abdelrahman Alhilou, Malin Ernberg

      Collaborations: PhD Akiko Shimada, Osaka University, Japan; Professor Brian Cairns, University of British Columbia, Canada; Professor Peter Svensson, Aarhus University, Professor Camilla Svensson, KI. 

      Example of high-power photomicrographs in four different colors: A,B, C and D
      Example of high-power photomicrographs, with a 40-fold magnification, from the masseter muscle of a healthy man. The photomicrograph shows fluorescent signaling of PGP 9.5 (A); NMDA-receptor2B (B); and Substance P (C) by masseter peripheral nerve fibers. (D) represent the composite image. Photo: n/a

      Mastication in Jaw Muscle Pain

      Collage: Teeth chewing chewing gum, comminution, teeth testing force-trancducers
      Chewing performance can be assessed by mixing, here illustrated with costume made two-colored chewing gums, by comminution, or by assessing different forces applied on force-trancducers. Photo: N/A

      PI: Nikolaos Christidis

      This project investigates if acute or chronic pain in the orofacial muscles or temporomandibular joints affect the human biting behavior or if absence of sensory input does affect the human biting behavior. It is a clinical/experimental study using patients and experimental pain settings, analyzing biting and chewing behavior with jaw-tracking, muscle EMG, and chewing performance by mixing and splitting different foods. The project started???

      Group member: Samaa Al-Sayegh

      Collaborations: PhD Anastasios Grigoriadis, PhD Krister Svensson, and PhD Abhishek Kumar, DentMed, KI. PhD Lars Fredriksson, Eastman Institute, Stockholm.

      Orofacial pain and jaw function in children and adolescents

        Occlusal applliances in different colors
        The use of occlusal appliances as treatment of painful temporomandibular disorders is supported by literature, but only for permanent dentitions/adults. By: Nikolaos Christidis

        PI: Nikolaos Christidis

        This multi-center project aims to investigate the prevalence, incidence, risk-factors, and knowledge-base among care-givers regarding temporomandibular disorders. Also, to investigate the effectiveness of different treatment modalities in children with primary or mixed dentition suffering from either TMD myalgia or arthralgia, and if these treatment modalities have any adverse effects on the mandibular development/growth.conducted in the Public Dental Health in Stockholm and Linköping. The project started 2019.

        Group members: Raghdah Abduljabbar, Ioanna Vasilatou, Sofia Louca Jounger

        Collaborations: PhD Georgios Tsilingaridis; PhD Lars Fredriksson, Senior Consultant Mathias Lemberger, Eastman Institute, Stockholm, Associate professor Pernilla Larsson-Gran, Folktandvården Druvan, Östergötland, PhD Amal Al-Khotani, Jeddah University, Saudi-Arabia.

          Learning dental and nursing literacy as part of professional knowing in academia

          PI: Nikolaos Christidis

          This is an observational study using interviews with thematic analysis that aims to map and analyze Swedish dental students’ writing in an academic setting, i.e. what these students are expected to read and write, how they are expected to read and write, and what they write. The project started

          Group member: Sofia Louca Jounger

          Collaborations: PhD Viveca Lindberg, Stockholm University; PhD Maria Christidis, Red Cross University College, Huddinge.

          Prediction of disease activity and TMJ in patients with juvenile idiopathic arthritis

          PI: Britt Hedenberg-Magnusson

          In this project we will evaluate the potential usefulness of the diagnostic criteria Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) in combination with panoramic and CT imaging in monitoring disease activity and severity in TMJ involvement in children and adolescents with JIA. We also aim to valuate if analyses of potential salivary biomarkers can be a useful tool in monitoring disease activity in JIA in general. The project stared 2013.

          Group members: Malin Collin, Nikolaos Christidis, Malin Ernberg

          Collaborations: Associate Professor Stefan Hagelberg, KI; Professor Thore Larheim and PhD Linda Arvidsson, Oslo University, Norway

          Research support

          • Clinical Scientist Training Program KI (Golnaz Barjandi).
          • Region Stockholm/KI – SOF
          • Region Uppsala
          • The Swedish Dental Association
          • The Swedish Rheumatism Association
          • Ministry of Health, Saudi Arabia